In the first 6 months of 2022 there have been 240 cases of acute hepatitis of unknown cause in young children in the UK. This may not sound like a large number, but it is, because these are “new” cases of hepatitis caused by something new, not the normal background cases of viral hepatitis we see normally. Most cases of hepatitis in children in the UK are caused by Hepatitis Viruses A-E, but in this outbreak the cause is something different.
 
In fact, the World Health Organisation say there have been over 650 cases reported from 33 countries Worldwide between 5th April and the 26th May, but this is likely to be an underestimate due to many countries not looking for specific causes of hepatitis, but rather assuming it is due to Hepatitis Viruses A-E because the tests to confirm the cause are not always routinely available.
 
The other striking thing about these cases, above and beyond the unknown cause, is that the hepatitis appears to be more severe than hepatitis normally is in children.
 
The UK has been investigating this outbreak for most of the year and has pretty thorough data from 1st January to the 3rd of May. In this period there were 163 cases of which 11 required liver transplants. No patients have died so far in the UK, but in the USA 20 of 109 cases required liver transplants, and 3 died. Needless to say, this is worrying, as severe liver failure or death from acute hepatitis in children is usually very, very, rare.
 
What is hepatitis and how does it present?
Hepatitis is inflammation of the liver. It presents with:

• Jaundice – yellowing of the skin and eyes due to the build up of bilirubin in blood which has a yellow colour (think of The Simpson’s and you won’t be far wrong!)
• Dark urine – as bilirubin gets into urine it makes the urine dark
• Pale grey poo – bilirubin is normally excreted into the gut making poo brown (although there are other reasons as well, but let’s not go there!) but if bilirubin is not excreted by the liver into the gut the poo stays pale and grey
• Itchy skin – caused by the build-up of bilirubin and bile salts in skin
• Muscles and joint pains
• Fever
• Nausea and vomiting
• Tiredness
• Loss of appetite
• Abdominal pain – especially right upper quadrant pain over the liver

 
Normally the liver is very good at recovering and regrowing after damage has been caused. Even the ancient Greeks knew this. In the Greek legends Prometheus was punished by Zeus because he stole fire to give back to mankind. He was chained to a rock in the Caucasus Mountains, and every day an eagle came and ate part of his liver. Each night, his liver would regrow, which meant he had to endure his punishment for eternity. Okay, the liver takes a bit longer than a night to regrow but you get the (very graphic!) picture.
 
In the case of severe liver failure, the damage to the liver is too much for the liver to cope with and it dies completely. In this situation the patient either gets a liver transplant, or they die; we do not have a machine that effectively performs the function of the liver in the way we do with kidneys and dialysis.
 
The other thing that is a bit weird about the current outbreak is that all the cases are in children, with nearly 60% being 3-5 years old. Cases do not appear to be occurring in adults suggesting adults are not susceptible or are immune to whatever is causing the hepatitis.
 
What are the current hypotheses?
A lot of work has been done to try and identify the cause of the hepatitis outbreak. The most common and consistent finding so far is the presence of Adenovirus DNA in the blood of about 70% of the patients. At the moment this is the top of the possible causes although it is not confirmed and Adenovirus infections in children are very common so it is possible this could be coincidental. At the moment nothing will be ruled out until it has definitely been shown to not be the cause.
 
The current possible hypotheses are:

• An unusual Adenovirus infection due to:
  • Abnormal patient response to the Adenovirus leading to hepatitis
  • Very high rates of population Adenovirus infection meaning the outbreak of hepatitis looks bigger than normal (lots of cases means relatively more “rare” complications)
  • Abnormal response to Adenovirus due to immune priming by SARS CoV2 which is also very common at the moment (SARS CoV2 is making patients respond to Adenoviruses in a weird way)
  • Abnormal response to Adenovirus due to coinfection with another as yet unidentified virus
  • Abnormal response to Adenovirus due to exposure to an unidentified toxin, drug or environmental chemical
• A new variant of Adenovirus
• A post-infection syndrome due to past SARS CoV2 infection
• A drug, toxin or environmental exposure (without blaming any viruses)
• A novel unknown pathogen yet to be discovered (oh goody, another new virus!!!)
• A new variant of SARS CoV2

 
Although the list of possible hypotheses is very long, the Adenovirus hypothesis is number 1.
 
Another bit of supporting evidence for the Adenovirus hypothesis is that in 27 of 35 children who had their Adenoviruses typed by molecular methods, the Adenovirus was shown to always be type 41F. Again, this doesn’t prove Adenovirus 41F is the cause, as it could just be the common Adenovirus circulating within the population at the moment, but it is suggestive that there might be something special about this particular virus.
 
So far, no toxin or drug has been found. Some background use of paracetamol (a hepatotoxic drug) has been found, but the levels in the patients is consistent with treatment doses not toxic doses.
 
The most important theory that has been excluded is that the cause might be the Covid vaccinations. IT IS NOT! These children (under 5 years old) are too young to have been vaccinated.
 
So, where are we now?
Well, the hunt for the cause continues. Paediatricians, Virologists and Microbiologists around the UK are on the look out for cases of unexplained hepatitis, especially in children. Any child with hepatitis (whatever the cause) should be notified to the Health Security Agency as soon as possible so they can continue to build up a picture of who is getting hepatitis and what they might have been exposed to. Children with hepatitis should have ALL these tests sent for possible causes:

• Serum for Hepatitis Viruses A-E
• Whole blood (EDTA, normally the purple tube) for Adenovirus PCR
• Throat swab for Adenovirus PCR

 
In the meantime, what can we do?
 
How to prevent infection
Even though we don’t know the cause of these cases of acute hepatitis in children we can have a pretty good guess at how to stop them.
 
Adenoviruses are spread by droplets, in the same way as SARS CoV2… so wash your hands regularly, don’t sneeze in people’s faces and cover your mouth when you cough! Oh, how quickly we forget… 

No, I’m serious… what is Covid? I hear it all the time. Someone coughs, is it Covid? Someone sneezes, is it Covid? Some say they feel a bit under the weather, is it Covid? I even had the discussion with my parents at the weekend… ECIC (aka my wife) has a bit of a cold and they say, “has she got Covid?”
 
So, what is Covid?
To start with, “Covid” isn’t anything. The actual name for the disease cause by the Severe Acute Respiratory Coronavirus type 2 (SARS CoV2) was Covid-19; it was an acronym for COronaVirus Infectious Disease 2019. But now it has been reduced to a snappier “Covid”.
 
I have also been asked if someone has “caught covid”…NO! You cannot catch Covid-19, you can catch SARS CoV2, that is the name of the virus. It is so reminiscent of the horror show that was HIV back in the 1980s… even senior health professionals thought you could catch AIDS (Acquired Immune Deficiency Syndrome) …NO! You cannot catch AIDS, you can catch Human Immunodeficiency Virus (HIV). Covid-19 and AIDS are the names of the clinical diseases, not the causative viruses.
 
So, when we think about Covid-19 being a disease, a group of symptoms if you like, then the question “what is Covid-19?” actually starts to make more sense. 

​What is Covid-19?
The original Covid-19 was a severe infection with SARS CoV2 characterised by high fever, cough, severe shortness of breath and hypoxia often requiring hospitalisation for respiratory support.
 
But we rarely see this pattern of infection with SARS CoV2 anymore. It has been a while since I have seen someone sick enough with SARS CoV2 infection to end up on ITU. Yet there are still about 80 patients a day with positive SARS CoV2 tests around the hospital, so what has happened?
 
The increase in immunity to SARS CoV2 from previous infection or vaccination has changed the symptoms of infection with SARS CoV2. In fact, the NHS website lists lots of symptoms of Covid-19 now… but are they all Covid-19?

• a high temperature or shivering (chills) – a high temperature means you feel hot to touch on your chest or back (you do not need to measure your temperature)
• a new, continuous cough – this means coughing a lot for more than an hour, or 3 or more coughing episodes in 24 hours
• a loss or change to your sense of smell or taste
• shortness of breath
• feeling tired or exhausted
• an aching body
• a headache
• a sore throat
• a blocked or runny nose
• loss of appetite
• diarrhoea
• feeling sick or being sick

 
It seems to me that the list of possible symptoms from infection with SARS CoV2 has become so broad that the term Covid-19 has probably become obsolete. ECIC has tested negative, but she has a new cough, shortness of breath, feels tired, has a sore throat, blocked nose blah blah blah… but she hasn’t got Covid-19 she has one of the many other “cold-like” illnesses we don’t name… she also didn’t get too much mollie-codling or sympathy either! Donuts, ice cream are allowed, and to just watch daytime TV and snooze in the afternoon… she is getting better… it’s probably an unnamed virus… it will pass.
 
Think about it. We don’t normally have a single name for all infections caused by a specific bacterium. We wouldn’t say a patient had “Staphylococciitis” (okay, I have just made that up), we would say they had had cellulitis, or septic arthritis, or osteomyelitis, or endocarditis, or one of the other infections caused by Staphylococcus aureus. The name of the infection is dependent on the symptoms… not the causative microorganism.
 
And we don’t call the other coronavirus related infections by any specific name; we don’t have Covid-92 for what was thought to be the cause of “Russian Flu” back in 1892.
 
I think we need to move on. I think still talking about Covid-19 is damaging. It is damaging because it dilutes our understanding of how severe the infection can be in non-immune people, and it increases the anxiety for those who have a mild or asymptomatic upper respiratory tract infection; some people still think everyone with COVID-19 dies!!!!!!!!
 
Personally, I think it is time to stop using the term Covid-19 EXCEPT as the name for the severe life-threatening acute respiratory infection that leads to people ending up on intensive care units. For everyone else we should use the term for their actual infection; upper respiratory tract infection (URTI), pharyngitis, pneumonia, acute coryzal illness (a cold).
 
To this we can then add the causative virus if we really, really, really, want to:

• URTI caused by SARS CoV2
• Pharyngitis caused by SARS CoV2
• Pneumonia caused by SARS CoV2
• Cold… no, just a cold, eat chicken soup, donuts, ice cream, whatever you like… it’s a cold and as “old housewives” say…you “feed a cold”…

 
But what do you think? Do you think the name Covid-19 still has a wider value? Or do you think it should be restricted to specific patients?
 
Or do you not care… it’s just pedantic Microbiologists who think about these things and everyone else has something better to do? 😊 Okay, fair enough…
 
That’s it, I’m not going to write another blog about Covid-19!

I can just imagine the conversation:
 
“Goldberger, I need you to go down South and investigate an outbreak” demanded the Surgeon General.
 
“Yes Sir!”, replied Dr Joseph Goldberger, “Errr, what outbreak am I investigating Sir?”
 
“The leprosy-like skin infection outbreak that no one has ever been able to discover a cause for of course, it’s affecting millions of people down there.”
 
“Yes Sir!” replied Dr Goldberger again, whilst probably thinking with a sinking heart “OMG, this sounds like a nightmare…”
 
But when you work for an organisation such as the US Public Health Service in 1915 and your boss tells you to do something you pack your bags and off you go. So he did…

If you were a Little Miss or Mr Man who would you be? Little Miss Naughty or Little Miss Fabulous? Mr Bump or Mr Perfect? Or would you be one of the brand new Little Miss or Mr Men; Little Miss Brave or Mr Calm? The choices seem almost endless! I like to think I’m Mr Clever, but ECIC thinks I’m more like Mr Silly… thanks a lot Little Miss Trouble!

“We have a septic lady who has just returned from a trip to India. She also has a headache and diarrhoea. We think she might have typhoid but want to cover for meningitis as well as this. What do you suggest?”
 
The Microbiologist listened as the Emergency Department (ED) Consultant expanded on the story with where exactly the patient had been in India, what she had been doing there and what pre-travel vaccinations she had had. It was a great presentation and showed that the Consultant had clearly been listening to the teaching on fever in a returning traveller that the Microbiologist had given the week before!
 
“Okay, she’s been to the North of India, we’d better cover for XDR typhoid as well as meningitis and other potential causes of sepsis. The best thing to do is start IV Meropenem 2g TDS, and if it’s not meningitis then we can reduce the dose to 1g later” replied the Microbiologist.
 
“Isn’t IV Ceftriaxone the normal first line for typhoid?” asked the ED Consultant.
 
“It is” replied the Microbiologist, “unless you have the XDR typhoid which is currently causing mayhem in Pakistan next to India, XDR is Ceftriaxone resistant and so you need Meropenem instead.”
 
“Crikey!” exclaimed the ED Consultant, “long gone are the days when I could treat this with Ampicillin…I’m sure Typhoid Mary would have accepted Ampicillin!”
 
“We all feel a little old these days, I find it’s more about the mileage not so much the years…!” said the Microbiologist.

“May I discuss a patient with you please?” asked the ward Doctor.
 
“You want to discuss a patient? Okay, but this telephone line is terrible” replied the Microbiologist, wondering whether the “new” telephone system in the hospital was really an “improvement”.
 
“Sorry, it’s a bit difficult to hear you” said the ward Doctor, “I wanted to discuss a patient with enlarged glands in the neck.”
 
“What?!” exclaimed the Microbiologist, “you think your patient has glanders! Why do you think they have glanders?”
 
“Yes, they have large glands …in their neck.”
 
“Glanders is extremely rare, and very severe, have you started antibiotics?”
 
“Yes, we want to start antibiotics.”
 
The telephone line was still terrible, and the Microbiologist was starting to get really worried. He looked at the number listed on the phone recognising it as the Acute Medical Unit where patients were admitted.
 
“I’m coming to you, wait for me there” said the Microbiologist putting down the phone.
 
“Blooming Microbiologist,” muttered the ward Doctor, “he just hung up on me!”
 
What is glanders?
Glanders is principally an infection of “solipeds” …that’s horses, donkeys and mules to you and me. It is caused by the bacterium Burkholderia mallei, a small, Gram-negative, oxidase positive, bacillus, that only replicates inside its living host being unable to survive in the environment. B. mallei is not to be confused with a similar bacterium I blogged about way, way, back in 2017 called Burkholderia pseudomallei which causes a condition called melliodosis and which is able to survive in the environment!

“Is that the Duty Microbiologist? Can I please discuss a patient with you and get your advice?” asked the Junior Doctor.
 
The Microbiologist nearly fell off his chair… people were rarely that polite when calling…
 
“Certainly, what can I help you with?” he replied, feeling immediately predisposed to being happy and helpful. (A very weird and unfamiliar feeling for the Microbiologist!)
 
“I have a complex patient who had a kidney transplant about 6 months ago who keeps getting UTIs. She has had a number of positive urine cultures and she feels better after being treated, but when the antibiotics stop, she quickly becomes symptomatic again. We’re wondering where we go from here. Should we try a longer course of antibiotics to see if that helps or would she benefit from antibiotic prophylaxis?”
 
The Microbiologist had been listening intently.
 
“This could be BK virus infection causing ureteral stenosis. Have you imaged the transplanted renal tract?”
 
“Beaky what virus?” asked the Junior.
 
And it had been going so well….

The Microbiologist sat quietly eating his lunch, partially hidden behind a pot plant in the staff canteen, when he sensed someone standing behind him. “Damn!” he thought, thinking he had hidden well enough to prevent his lunch being interrupted with any clinical questions... but clearly not.
 
Looking around he met the gaze of the Cardiology Registrar who was clearly waiting to make eye contact before launching into “the patient’s story”!
 
…“I have a patient in her early twenties who came in with a fever and a rash, but over the last few days she has started to go into heart failure”.
 
The Registrar had been in the Microbiologist’s teaching session early in the week, and had clearly “swotted up” after being asked questions he didn’t know the answers too.
 
The Cardiology Registrar then delivered the “piece de resistance” and declared “I think this might be Rheumatic Fever”.

“Okay, this is going to sound odd, but can we test a baby for RSV?” asked the Paediatrician.
 
“You do realise it’s July, don’t you? I mean I know we’ve all been locked in our houses for months, it’s raining and the radio played a Christmas song this morning…but it’s still summer!” exclaimed the Microbiologist.

“I have a patient in his 40s who has been coughing for several weeks and is starting to get fed up. The cough is keeping him, and his wife, awake, so he’s taken to sleeping in the spare room in order to give her some respite but it’s not ideal. I’ve done a chest x-ray and it looks okay, and he’s not really coughing anything up in order to send to it to the lab for culture. What antibiotics do you think I should give?” said the GP.